Project Summary Traumatic events are common. Posttraumatic Stress Disorder (PTSD) is one of the most common disorders resulting from trauma, tending to co-occur with increased alcohol consumption (i.e., alcohol quantity x frequency [AQF]) and AUD. Much of this research on the comorbidity of PTSD and alcohol phenotypes has focused on PTSD-AUD. As increased consumption of alcohol is associated with AUD, research is needed to determine whether the same etiologic processes underlying PTSD-AUD comorbidity are those underlying PTSD and AQF. Although the pathways by which shared risk for these phenotypes unfolds is unclear, longitudinal and experimental research suggests effects of distress tolerance (DT), the perceived ability to withstand negative emotional states, and anxiety sensitivity (AS), cognitive appraisal of anxiety symptoms as having harmful physical, mental, or social consequences, on PTSD and alcohol phenotypes. Additionally, genetic influences on PTSD and AQF/AUD may underlie risk for DT and AS. Thus, the goals of this K01 application are threefold: First, the proposed study will use large-scale molecular data and employ cutting-edge methods to investigate cross phenotype prediction between PTSD-AQF, and PTSD-AUD, and direction of effect between PTSD and AQF/AUD. Second, this study proposes to investigate the associations between DT and AS, and risk for PTSD, AUD, and comorbid PTSD-AUD. Finally, via an Exploratory Aim, it will examine whether genetic risk for AQF, AUD, and PTSD are associated with DT and AS, and if socioeconomic status and social support moderate these effects. To achieve these aims, the candidate will be assisted by her mentorship team in the completion of a comprehensive training plan that maps onto these three goals. Specifically, this K01 application will allow the candidate to receive training in cutting edge genetic methods (training goal 1), laboratory-based paradigms and psychophysiological data (training goal 2), the psychiatric and social epidemiology of stress-related phenotypes (training goal 3), and professional development (training goal 4). With the help of the multidisciplinary mentorship team, this K01 award will allow the candidate to integrate large-scale genetic association findings with laboratory-based self-report, behavioral, and psychophysiological measures, to predict risk for PTSD-AQF/AUD co-occurrence for those of varying SES levels and varying social support. The proposed study represents an important step forward in clarifying risk factors and mechanisms of this costly co-occurrence. The environment where the candidate will be trained is ideal for the candidate's long-term goal of understanding the etiology of co-occurring PTSD and alcohol phenotypes to improve prevention/intervention programs. This goal is in line with key NIAAA's research priorities, involving identifying mechanisms underlying AUD and co-occurring mental health problems while integrating genomic and non-genomic factors.